pH敏感多肽胶束作为药物载体的分子设计与结构调控

pH sensitive micelles self-assembled from amphiphilic have been considered as promising hydrophobic drug carriers. In this proposal, novel amphiphilic polypeptides assembled micelles will be designed and developed for anticancer drug delivery. The mechanism and method of molecular design of drug carrier and structural optimization of drug loaded nanoparticles will be further studied. Specific Aim 1. To develop a methodology which can be used for molecular design of drug carriers according to the properties of different drug molecules. Specific Aim 2. To investigate the multi-scale structure-performance relationship of polymer/drug molecules, mesoscale structures of drug loaded nanoparticles, and drug release properties. Specific Aim 3. To develop mathematical modelings from the structural parameters and drug release profies, which can be used to predict the drug release properties. In this proposal, doxorubicin and paclitaxel will be used as model drugs. Amphiphilic polypeptides will be designed and optimized for hydrophobic anticancer drug delivery. Computer simulations, experimental techniques, as well as theoretical analysis will be uesd to reveal the key issues, such as the the structure-performance relationship of polymer/drug molecules, mesoscale structures of drug loaded nanoparticles, and drug release properties, structural control of drug loaded nanoparticles, etc. The results will set foundation for molecular design and structural control in developing novel drug delivery systems.

pH敏感纳米胶束作为疏水性药物的载体，在药物传输系统中有很好的应用前景。本项目研究新型两亲多肽胶束作为抗癌药物载体的分子设计及其载药颗粒结构调控的原理和方法。重点研究：（1）根据药物的不同特性进行载体材料的分子设计的方法；（2）分子结构、载药颗粒的介观结构和宏观的释放性能之间的不同尺度间的定量构效关系；（3）载药胶束结构与药物释放性能之间的定量关系数学模型。本项目选择阿霉素与紫杉醇为模型药物，设计、优化与合成pH敏感两亲性多肽分子作为疏水性抗癌药物的载体。并综合利用计算机模拟、实验技术和理论分析来揭示分子结构、载药颗粒的介观结构与宏观性能之间的定量构效关系、纳米粒结构调控等关键问题，为开发新型纳米载药颗粒中的分子设计与载药颗粒结构调控提供理论基础与关键技术。

本项目旨在探索两亲性高分子胶束载药系统中所涉及的结构性能关系研究。研究了新型两亲胶束作为抗癌药物载体的分子设计及其载药微颗粒结构调控的原理与方法。以阿霉素为模型药物，pH敏感两亲多肽分子中，疏水基选择DHA或丙氨酸，亲水基选择精氨酸或赖氨酸，pH敏感链段选择组氨酸。设计并优化了多肽分子的组成、结构。通过综合运用多尺度计算机模拟、实验技术与理论分析，研究了分子结构、纳米粒的介观结构与宏观结构之间的构效关系等关键问题。为开发新型纳米载药颗粒中的分子设计与载药颗粒的结构调控提供了研究思路与方法，促进新型纳米粒载药系统的开发与应用。